https://scholars.lib.ntu.edu.tw/handle/123456789/565269
標題: | 5-Aroylindoles Act as Selective Histone Deacetylase 6 Inhibitors Ameliorating Alzheimer's Disease Phenotypes | 作者: | Lee H.-Y. Fan S.-J. Huang F.-I. Chao H.-Y. Hsu K.-C. Lin T.E. Yeh T.-K. Lai M.-J. Li Y.-H. Huang H.-L. CHIA-RON YANG Liou J.-P. |
公開日期: | 2018 | 卷: | 61 | 期: | 16 | 起(迄)頁: | 7087-7102 | 來源出版物: | Journal of Medicinal Chemistry | 摘要: | This paper reports the development of a series of 5-aroylindolyl-substituted hydroxamic acids. N-Hydroxy-4-((5-(4-methoxybenzoyl)-1H-indol-1-yl)methyl)benzamide (6) has potent inhibitory selectivity against histone deacetylase 6 (HDAC6) with an IC50 value of 3.92 nM. It decreases not only the level of phosphorylation of tau proteins but also the aggregation of tau proteins. Compound 6 also shows neuroprotective activity by triggering ubiquitination. In animal models, compound 6 is able to ameliorate the impaired learning and memory, and it crosses the blood-brain barrier after oral administration. Compound 6 can be developed as a potential treatment for Alzheimer's disease in the future. ? Copyright 2018 American Chemical Society. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85050635071&doi=10.1021%2facs.jmedchem.8b00151&partnerID=40&md5=0e6278aafb36eae87b8307658802ff46 https://scholars.lib.ntu.edu.tw/handle/123456789/565269 |
ISSN: | 222623 | DOI: | 10.1021/acs.jmedchem.8b00151 | SDG/關鍵字: | 3 [3 [5 (3,4 dimethoxy benzoyl)indole 1 sulfonyl]phenyl] n hydroxy acrylamide; 3 [3 [5 (4 fluoro benzoyl)indole 1 sulfonyl]phenyl] n hydroxy acrylamide; 4 [5 (3,4 dimethoxy benzoyl)indol 1 ylmethyl] n hydroxy benzamide; 4 [5 (4 chloro benzoyl)indol 1 ylmethyl] n hydroxy benzamide; 4 [5 (4 fluoro benzoyl)indol 1 ylmethyl] n hydroxy benzamide; 5 aroylindole derivative; histone deacetylase 1; histone deacetylase 2; histone deacetylase 3; histone deacetylase 6; histone deacetylase inhibitor; hydroxamic acid derivative; indole derivative; n hydroxy 3 [3 [5 (3 methoxy benzoyl)indole 1 sulfonyl]phenyl]acrylamide; n hydroxy 3 [3 [5 (3,4,5 trimethoxy benzoyl)indole 1 sulfonyl]phenyl]acrylamide; n hydroxy 3 [3 [5 (4 methoxy benzoyl)indole 1 sulfonyl]phenyl]acrylamide; n hydroxy 3 [3 [5 (4 methyl benzoyl)indole 1 sulfonyl]phenyl]acrylamide; n hydroxy 3 [4 [5 (3,4,5 trimethoxy benzoyl)indol 1 ylmethyl]phenyl]acrylamide; n hydroxy 3 [4 [5 (3,4,5 trimethoxy benzoyl)indole 1 sulfonyl]phenyl]acrylamide; n hydroxy 3 [4 [5 (4 methoxy benzoyl)indol 1 ylmethyl]phenyl]acrylamide; n hydroxy 3 [4 [5 (4 methoxy benzoyl)indole 1 sulfonyl]phenyl]acrylamide; n hydroxy 4 [5 (3 methoxy benzoyl)indol 1 ylmethyl]benzamide; n hydroxy 4 [5 (3,4,5 trimethoxy benzoyl)indol 1 ylmethyl]benzamide; n hydroxy 4 [5 (4 methoxy benzoyl)indol 1 ylmethyl]benzamide; n hydroxy 4 [5 (4 methyl benzoyl)indol 1 ylmethyl]benzamide; neuroprotective agent; nootropic agent; tau protein; trichostatin A; unclassified drug; vorinostat; HDAC6 protein, human; histone deacetylase 6; histone deacetylase inhibitor; hydroxamic acid; indole derivative; neuroprotective agent; tau protein; Alzheimer disease; animal cell; animal experiment; animal model; animal tissue; Article; blood brain barrier; brain-to-plasma ratio; cognitive defect; comparative study; concentration response; controlled study; down regulation; drug blood level; drug brain level; drug selectivity; drug synthesis; elevated plus maze test; enzyme activity; enzyme inhibition; histone ubiquitination; human; human cell; IC50; learning disorder; male; maximum tolerated dose; memory disorder; Morris water maze test; neuroprotection; nonhuman; protein aggregation; protein phosphorylation; rat; SH-SY5Y cell line; Alzheimer disease; animal; binding site; cell line; chemistry; cognition assessment; disease model; drug effect; female; metabolism; molecular docking; phosphorylation; Sprague Dawley rat; synthesis; transgenic mouse; ubiquitination; Wistar rat; Alzheimer Disease; Animals; Binding Sites; Blood-Brain Barrier; Cell Line; Disease Models, Animal; Female; Histone Deacetylase 6; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Indoles; Male; Memory and Learning Tests; Mice, Transgenic; Molecular Docking Simulation; Neuroprotective Agents; Phosphorylation; Rats, Sprague-Dawley; Rats, Wistar; tau Proteins; Ubiquitination |
顯示於: | 藥學系 |
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